The proposed research focuses on the problem of separation of racemic mixtures of biochemically important analyses into pure enantiomers. Two approaches to this problem will be pursued in parallel. Ultra-high surface area inorganic solids will be intercalated with chiral selector molecules that are capable of binding selectively to a single analyte enantiomer. Initially this work will concentrate on solids such as zeolites and layered metal phosphates, which have internal surface areas approximately ten times higher than conventional chiral chromatographic supports. Prior work has shown that these materials can be intercalated with chiral selectors, and that they have an unprecedented capacity for reversible binding of model analyses. The initial phase of this study will involve optimization of these materials for batchwise separation of pharmaceutically interesting enantiomers. Novel chiral selector cyclophanes will be synthesized, with the aim of overcoming current limitations that stem from host "pre-organization". Established techniques will be used to grow pellicular films of these high surface area hosts on chromatographic support particles; the kinetics of analyte equilibration with these particles, and preparative HPLC separation of enantiomers, will then be studied. The second approach to this problem involves shape-selective binding and "template" effects in surface monolayer films. The aim of this aspect of the work is to create a scientific underpinning for the design of surfaces that bind enantiomers selectively, based on cooperative, intermolecular noncovalent bonds. Chiral molecular interactions play a central role in nearly all life processes. Most biomedically important drugs are chiral, and of those made synthetically, most are sold as racemic mixtures of optical isomers. Generally, only one isomer is therapeutically valuable, and the others may have undesirable side effects. The availability of general methods for chiral separations on a preparative scale is essential for individual screening of the optical isomers of new synthetic drugs. The proposed work will develop promising materials for preparative chiral separations.